The long-term goal of the project is to identify signals that mediate the circadian regulation of behavior. Twenty-four hour (circadian) rhythms are strongly expressed in the behavior of animals and humans. For example, the homeostatic regulation of sleep is modulated by circadian output so that sleep is consolidated and phased to occur at a particular time of day. A circadian pacemaker in the hypothalamus, the suprachiasmatic nucleus (SCN), drives the circadian modulation of sleep as well as rhythms in other behaviors and in neuroendocrine and metabolic functions. The phasing of these rhythms is regulated by light via entrainment of the SCN and retinal projections that are distinct from the visual system. Non-visual projections also mediate acute effects of light on behavior and neuroendocrine function. Little is known about the output mechanisms for the circadian regulation of behavior or for the acute, non-visual effects of light. SCN transplant experiments show that an SCN signal can affect downstream targets for the control of activity by diffusion from the third ventricle. Previously, we infused candidate molecules into the third ventricle of hamsters, and found that an SCN peptide, transforming growth factor alpha (TGFalpha) strongly inhibits wheel-running activity. TGF-alpha could mediate both the acute effects of light on behavior as well as the circadian modulation of behavior. In this project we will test two hypotheses: 1. That TGFalpha is a physiologically important output signal of the SCN, and 2. That a specific hypothalamic structure, the subparaventricular zone, is an essential target for SCN output and the acute effects of light. In addition, the same methods used to identify TGFalpha will be used to evaluate the role of other SCN peptides as output signals. An understanding of SCN output may allow the development of therapies for the treatment of abnormal sleep timing and consolidation. In addition, identifying mechanisms for the acute effects of light may lead to a better understanding of light therapy that is commonly used to treat mood disorders.